AUTHOR=Gong Jie , Wang Xin , Zhu Chenwen , Dong Xiaohua , Zhang Qinxin , Wang Xiaoning , Duan Xuchu , Qian Fuping , Shi Yunwei , Gao Yu , Zhao Qingshun , Chai Renjie , Liu Dong 

TITLE=Insm1a Regulates Motor Neuron Development in Zebrafish

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=10

YEAR=2017

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00274

DOI=10.3389/fnmol.2017.00274

ISSN=1662-5099

ABSTRACT=<p>Insulinoma-associated1a (insm1a) is a zinc-finger transcription factor playing a series of functions in cell formation and differentiation of vertebrate central and peripheral nervous systems and neuroendocrine system. However, its roles on the development of motor neuron have still remained uncovered. Here, we provided evidences that <italic>insm1a</italic> was a vital regulator of motor neuron development, and provided a mechanistic understanding of how it contributes to this process. Firstly, we showed the localization of <italic>insm1a</italic> in spinal cord, and primary motor neurons (PMNs) of zebrafish embryos by <italic>in situ</italic> hybridization, and imaging analysis of transgenic reporter line <italic>Tg(insm1a: mCherry)</italic><sup><italic>ntu805</italic></sup>. Then we demonstrated that the deficiency of <italic>insm1a</italic> in zebrafish larvae lead to the defects of PMNs development, including the reduction of caudal primary motor neurons (CaP), and middle primary motor neurons (MiP), the excessive branching of motor axons, and the disorganized distance between adjacent CaPs. Additionally, knockout of <italic>insm1</italic> impaired motor neuron differentiation in the spinal cord. Locomotion analysis showed that swimming activity was significantly reduced in the <italic>insm1a</italic>-null zebrafish. Furthermore, we showed that the <italic>insm1a</italic> loss of function significantly decreased the transcript levels of both <italic>olig2</italic> and <italic>nkx6.1</italic>. Microinjection of <italic>olig2</italic> and <italic>nkx6.1</italic> mRNA rescued the motor neuron defects in <italic>insm1a</italic> deficient embryos. Taken together, these data indicated that <italic>insm1a</italic> regulated the motor neuron development, at least in part, through modulation of the expressions of <italic>olig2</italic> and <italic>nkx6.1</italic>.</p>